Jordan B. Renner

Lifetime risk of symptomatic knee osteoarthritis

OBJECTIVE To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI). METHODS The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age >or=45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990-1997) and first followup (1999-2003) were analyzed. RESULTS The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0-49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4-65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese. CONCLUSION Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.

Prevalence of Hip Symptoms and Radiographic and Symptomatic Hip Osteoarthritis in African Americans and Caucasians: The Johnston County Osteoarthritis Project

Objective. To report contemporary estimates of the prevalence of hip-related osteoarthritis (OA) outcomes in African Americans and Caucasians aged ≥ 45 years. Methods. Weighted prevalence estimates and their corresponding 95% confidence intervals for hip symptoms, radiographic hip OA, symptomatic hip OA, and severe radiographic hip OA were calculated using SUDAAN® for age, race, and sex subgroups among 3068 participants (33% African Americans, 38% men) in the baseline examination (1991–97) of The Johnston County Osteoarthritis Project, a population-based study of OA in North Carolina. Radiographic hip OA was defined as Kellgren-Lawrence radiographic grade ≥ 2, moderate/severe radiographic hip OA as grades 3 and 4, and symptomatic hip OA as hip symptoms in a hip with radiographic OA. Results. Hip symptoms were present in 36%; 28% had radiographic hip OA; nearly 10% had symptomatic hip OA; and 2.5% had moderate/severe radiographic hip OA. Prevalence of all 4 outcomes was higher in older individuals; most outcomes were higher for women and African Americans. Conclusion. African Americans in this population do not have a lower prevalence of hip-related OA outcomes as previous studies suggested. Increasing public and health system awareness of the relatively high prevalence of these outcomes, which can be disabling, may help to decrease their effects and ultimately prevent them.

Increased Rate of Fractures and Severe Kyphosis: Sequelae of Living into Adulthood with Cystic Fibrosis

Cystic fibrosis is the most common fatal autosomal recessive genetic disease in white persons; it affects approximately 30 000 Americans and a similar number of Europeans [1]. Cystic fibrosis mutations occur in approximately 1 of every 2500 live births in the white population and lead to death or lung transplantation in more than 500 persons annually in the United States alone [2]. Although respiratory disease is the greatest cause of illness and death in patients with cystic fibrosis, improved therapy for chronic pulmonary infection has markedly extended life expectancy and has led to the discovery of myriad other problems that afflict these patients [3]. Osteoporosis, in particular, increases pain and debilitation in patients with cystic fibrosis as they live into adulthood. Patients with cystic fibrosis have increased risk for osteoporosis as a result of multiple factors [4]. Poor nutrition, pancreatic insufficiency, reduced absorption of calcium and vitamin D, reduced physical activity, delayed and reduced production of sex steroids, use of corticosteroids, and increased circulating concentrations of osteoclast-activating factors (such as tumor necrosis factor- and interleukin-1) may all cause reduced bone mineral density in patients with cystic fibrosis. Young patients with cystic fibrosis invariably fail to reach peak bone mass [5-10], and this contributes to low bone mineral density in adulthood. Unbalanced bone formation and resorption [11], caused by accelerated bone loss, may lead to further bone demineralization in early adulthood. Both increased bone resorption and decreased bone formation probably play a role in osteoporosis in cystic fibrosis [8, 12, 13]. Osteoporosis in patients with cystic fibrosis is well documented [5-10, 12-16]. Hahn and colleagues [5] were the first to show low bone mineral density (mean reduction, 15%) in the distal radii of these patients. In the past decade, reductions in bone mineral density for the femur (mean decrease, 11.1%), lumbar spine (mean decreases, 12.5% to 35%), and total body (mean decrease, 10%) [6, 12, 14] have been reported in adults with cystic fibrosis. Henderson and Madsen [7] recently found that patients with cystic fibrosis had low bone mineral density in childhood and that it worsened with age. The average z-scores for the lumbar spine were 0.39 for children aged 5 to 8 years, 0.99 for children aged 8 to 12 years, and 1.69 for children aged 12 to 18 years. Taken together, these results show that osteopenia may occur as early as the first decade of life in patients with cystic fibrosis and that bone loss accelerates during adolescence and early adulthood. Although low bone mineral density in cystic fibrosis has attracted considerable attention, data on the complications of osteoporosis, including fractures and kyphosis, are limited. Despite low bone mineral density and anecdotal reports of increased fracture rates [9, 14, 15, 17-20], no reports have documented significant increases in fracture rates in adults with cystic fibrosis. It has been suggested that the decreased activity level that accompanies progressive cystic fibrosis offers a protective influence with respect to the occurrence of fractures. Our main goal was to quantitate the clinical sequelae of osteoporosis, namely, fractures and kyphosis, in a large group of adults with cystic fibrosis to test the hypothesis that fracture rates and kyphosis angles are greater in patients with cystic fibrosis than in the general population. A second goal was to investigate the role of potentially important clinical variables in the pathogenesis of osteoporosis in cystic fibrosis. Methods Patients The study sample consisted of 70 adults (older than 18 years of age) with advanced cystic fibrosis who were referred for lung transplantation at the University of North Carolina between January 1994 and December 1996. The Committee on Human Research (IRB #96-Med-336) approved this retrospective cohort study and required verbal consent from participating patients. Cystic fibrosis was diagnosed by elevated sweat chloride concentrations and an appropriate clinical picture. All patients had end-stage lung disease and an anticipated survival of less than 2 to 3 years [21]. Fracture History The history, date, and mechanism of fracture were determined by personal interviews done using methods similar to those of the National Health Interview Study [22]. Fractures were required to have patient report of radiographic confirmation at the time of the fracture, but we did not review these radiographs. Confirmation of long-bone fractures required patient report of treatment with casting. Fractures occurring between birth and 6 years of age were not assessed because most patients were unable to provide accurate histories for those years. The number of years that each patient was at risk for fracture was summed by age interval to determine the total number of patient-years for this cohort. All patients were asked to give their date of puberty; to give a detailed history of corticosteroid use (expressed as cumulative dose of prednisone in grams); to state whether they had received therapy for osteoporosis; and, if they were female, to state whether and when they had had oligomenorrhea. Bone Densitometry Bone mineral density was measured in all patients by a single, registered radiologic technologist using dual-energy x-ray absorptiometry (Hologic QDR 1000/W, Waltham, Massachusetts) [23]. Lumbar spine (L1-L4), nondominant femoral neck, and total-body bone mineral densities were measured; measurements were expressed in grams of bone mineral per cm2 of bone. Quality control was maintained by daily scanning of an anthropomorphic spine phantom. The coefficient of variation for our Hologic QDR 1000/W densitometer is 0.3%, and the reference limits for variation are 1.5%. Results were expressed as T-scores, which are the number of SDs that the bone mineral density measurement is above (positive value) or below (negative value) expected peak bone mass. The age at which peak bone mass is achieved differs slightly for each site but is usually between 20 and 30 years. Using World Health Organization guidelines, we defined osteopenia as a T-score greater than 2.5 and 1.0 or less. Osteoporosis was defined as a T-score of 2.5 or less [24]. Normal bone mineral density was defined as a T-score of 0 1. Laboratory Measurements Serum calcium, phosphorus, alkaline phosphatase, and creatinine concentrations were measured with an automatic analyzer (Hitachi 911, Boehringer Mannheim, Indianapolis, Indiana). Vitamin D metabolites were extracted from serum specimens (obtained while patients were fasting) with column chromatography and were measured with radiobinding assays (Nichols Institute, Raleigh, North Carolina). The 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D assays had sensitivities of 5 pg/mL and 5 ng/mL, respectively. Testosterone levels were measured by using a competitive radioimmunoassay (Diagnostics Product Corp., Los Angeles, California). Genotype analysis for the 15 most common CFTR mutations was done by using published methods [25]. Radiographic Analysis Screening of the most recent posteroanterior and lateral chest radiographs for the extent of thoracic kyphosis as well as rib and vertebral body fractures was done by a single musculoskeletal radiologist on 65 patients (5 patients did not undergo radiography at the University of North Carolina). Thoracic kyphosis was measured from the second or third to the twelfth thoracic vertebral body by using a modification of the method of Cobb [26]. The number of vertebral compression fractures was also determined from the lateral radiograph by measuring anterior and posterior vertebral body height and expressing the difference as a percentage [27]. The posteroanterior chest radiograph was examined for the presence of rib fractures. Nonacute fractures appeared as focal deformities in the rib contour with varying degrees of reparative bone formation. Statistical Analysis Analyses were done with SAS software (version 6.12, SAS Institute, Cary, North Carolina) [28], and significance was based on two-tailed tests with a P value less than 0.05. Discrete variables are summarized as percentages, and continuous variables are summarized as means SD. Nonparametric methods were used when the distribution of the continuous variable was skewed. Student t-tests were used to compare differences in all clinical and anthropomorphic variables except fracture rates [29]. Relationships between spine and femur T-scores and seven continuous variables-age, age at puberty, cumulative steroid dose, body mass index, FEV1, FVC, and vitamin D levels-were assessed with either the Pearson or Kendall correlation coefficients [30]. Backward stepwise regression analysis was used to determine the multivariate relation between spine and femur T-scores and the aforementioned predictors. Clinical predictors and T-scores were compared, using the Kruskal-Wallis test, by dividing the patients into three groups: those without fractures, those with one fracture, and those with more than one fracture. This was done to determine whether differences existed between groups. Using spine or femur z-scores (the number of SDs that a bone mineral density measurement was above or below that of age- and sex-matched normal controls) rather than T-scores gave similar results (data not shown) because most patients were in the age range at which peak bone mass is expected. For the analysis of fractures and kyphosis angles, patients were grouped by age to conform with published databases (normal databases are based on age) [22, 31]. Two separate fracture rate analyses were done: In one, all fractures were used as the numerator; in the other, all persons with any fracture were used as the numerator. The latter analysis was done to eliminate the possibility that fracture clustering had affected the results. We used person-years as the denominator fo

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: The Johnston county osteoarthritis project

OBJECTIVE To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. METHODS Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade > or = 2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models. RESULTS Serum COMP levels were significantly elevated (P = 0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/- 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 +/- 487.47 ng/ml versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P = 0.0047), knee OA laterality (P = 0.0043), and number of knee and hip joints involved (P = 0.0001). There was no significant difference in serum COMP levels by gender or obesity. CONCLUSION We demonstrate that in a population-based sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.

One in four people may develop symptomatic hip osteoarthritis in his or her lifetime

OBJECTIVE To estimate the lifetime risk of symptomatic hip osteoarthritis (OA). DESIGN We analyzed data from the Johnston County Osteoarthritis Project [a longitudinal population-based study of OA in North Carolina, United States (n=3068)]. The weighted baseline sample comprised 18% blacks and 54% women, and the mean age was 63 years (range=45-93). Symptomatic hip OA was defined as a Kellgren-Lawrence (K-L) radiographic score of ≥ 2 (anterior-posterior pelvis X-rays) and pain, aching or stiffness on most days, or groin pain, in the same hip. Lifetime risk, defined as the proportion who developed symptomatic hip OA in at least one hip by age 85, among people who live to age 85, was modeled using logistic regression with repeated measures (through generalized estimating equations). RESULTS Lifetime risk of symptomatic hip OA was 25.3% [95% confidence interval (CI)=21.3-29.3]. Lifetime risk was similar by sex, race, highest educational attainment, and hip injury history. We studied lifetime risk by body mass index (BMI) in three forms: at age 18; at baseline and follow-up; and at age 18, baseline and follow-up and found no differences in estimates. CONCLUSION The burden of symptomatic hip OA is substantial with one in four people developing this condition by age 85. The similar race-specific estimates suggest that racial disparities in total hip replacements are not attributable to differences in disease occurrence. Despite increasing evidence that obesity predicts an increased risk of both hip OA and joint replacement, we found no association between BMI and lifetime risk.

Self-reported functional status in osteoarthritis of the knee in a rural southern community : The role of sociodemographic factors, obesity, and knee pain

OBJECTIVE This study examined the roles of sociodemographic factors (age, race, gender, education, marital status), obesity, and severity of radiographic knee osteoarthritis (OA) and knee pain on self-reported functional status. METHODS The sample included 1,272 African-American and Caucasian individuals, aged 45 years or older, from the Johnston County Osteoarthritis Project. Analysis of variance was used to assess variation in mean Health Assessment Questionnaire (HAQ) scores by the above variables. RESULTS Mean HAQ scores differed by severity of radiographic knee OA and knee pain, obesity, and all demographic factors (P < 0.0001), except race. Only age, female sex, obesity, and knee pain severity were independent effects (P < 0.0009). Disability associated with knee pain varied by both radiographic knee OA severity and obesity. CONCLUSIONS Knee pain severity was more important than radiographic knee OA severity in determining disability. Obesity was independently associated with disability and compounded disability from knee pain. Studies of disability in knee OA should include assessment of obesity, severity of radiographic knee OA, and severity of knee pain, as well as their interactions.

Anthropometric measures, body composition, body fat distribution, and knee osteoarthritis in women

Objective: Increased BMI is a well‐recognized risk factor for radiographic knee osteoarthritis (rKOA); however, the contributions of the components of body composition, body fat distribution, and height to this association are not clear.

Comparative evaluation of three semi-quantitative radiographic grading techniques for hip osteoarthritis in terms of validity and reproducibility in 1404 radiographs: report of the OARSI-OMERACT Task Force

OBJECTIVE The objective of this work was to compare the measurement properties of three categorical X-ray scoring methods of knee osteoarthritis (OA), both on semiflexed and extended views. METHODS In data obtained from trials and cohorts, X-rays were graded using Kellgren and Lawrence (KL), the OA Research Society International (OARSI) joint space narrowing score, and measurement of joint space width (JSW). JSW was analyzed as a categorical variable. Construct validity was assessed through logistic regression between X-ray stages and Western Ontario and McMaster Universities OA Index. Inter-observer reliability was assessed in 50 subjects for extended views by weighted kappa. Intra-observer reliability and sensitivity to change were assessed separately for extended and semiflexed views in 50 patients who had both views performed, over a 30-month interval, by weighted kappa and standardized response mean (SRM). RESULTS Extended views were available from three trials and two cohorts (1759 X-rays), including one trial in which both extended and semiflexed views (antero-posterior) were obtained. Correlation with clinical parameters was low for the three scoring methods, except for the single community-based cohort. Inter-rater reliability was higher for categorical JSW in extended views (kappa, 0.86 vs 0.56 and 0.48 for KL and OARSI, respectively). Intra-rater reliability was higher for categorical JSW, both in extended views (0.83 vs 0.61 and 0.71) and in semiflexed views (0.89 vs 0.50 and 0.67). Sensitivity to change was also higher for categorical JSW, particularly in semiflexed views (SRM, 0.49 vs 0.22 and 0.34). CONCLUSION These results indicate categorical JSW, in particular on semiflexed views, may be the preferred method to evaluate structural severity in knee OA clinical trials.

Abnormal bone turnover in cystic fibrosis adults.

Abstract: Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 ± 18.6% predicted) and malnutrition (BMI: 20.0 ± 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 ± 60.0 vs 49.0 ± 24.2 nm BCE/mmol creatinine, p= 0.0006) and free deoxypyridinoline (7.3 ± 5.0 vs 5.3 ± 1.9 nM/mM, p= 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 ± 11.3 vs 21.8 ± 7.0 U/l, p<0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p= 0.007) and 25-hydroxyvitamin D levels were depressed (p= 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.

Soy Isoflavones: No Effects on Bone Mineral Content and Bone Mineral Density in Healthy, Menstruating Young Adult Women after One Year

Background: The effects of isoflavone-enriched soy protein on human bone mineral content (mass) and density in healthy, menstruating young adult females have not been examined in a comparative prospective investigation. Peri- and post-menopausal women have been reported to show beneficial effects of isoflavones on bone measurements. Therefore, young women may also be able to improve their accrual of peak bone mineral content (BMC) and bone mineral density (BMD) during the early adult years of bone consolidation with an isoflavone-enriched diet. Objectives: In this controlled, double-blind intervention, we tested the hypothesis that an isoflavone-rich soy protein diet increases BMC and BMD in young adult females over a period of one year in comparison to a control group receiving soy protein that has isoflavones removed. Design: Young healthy women of any ethnic background, 21 to 25 years of age, were divided into two groups, placebo (n = 13) and supplement (n = 15). The soy protein supplement was enriched with isoflavones (∼90 mg of total isoflavones/day), whereas the control protein diet was isoflavone-deficient, even though it contained the same amount of soy protein and other ingredients as the isoflavone-rich diet. Dual-energy x-ray absorptiometric (DXA) measurements of BMC and BMD were made at baseline and at 6 and 12 months. DXA estimates of body composition, including fat mass and lean body mass, were generated from whole-body BMC measurements. BMI was calculated as weight (kg) over height (m) squared. Physical activity was assessed, and three-day dietary records were taken at entry (baseline) and at 6 and 12 months. Results: No changes in BMD after 12 months were found in either the isoflavone-treated (treatment) group or the isoflavone-deficient (control) group. Other variables also remained essentially constant over the 12-month period, including normal menstrual patterns in both the treatment and control groups. Conclusions: The isoflavone-rich soy preparation had no effects on BMC and BMD over a 12-month period in young healthy adult females with normal menses. An isoflavone-rich supplement appears to have little or no effect on bone in young adult women with normal ovarian function, at least over this 12-month study period.